The fundamental question of how cells of bones and teeth assemble and mineralize their respective matrices in such a coordinated and superbly biofunctional way is still largely unanswered. The Protein Chemistry Unit has been performing structure-function analyses on several of the non collagenous proteins. One approach has been to determine the amino acid sequences within a protein that are involved in the interactions of matrix components or between cells and the surrounding matrix. Decorin is small proteoglycan thought to be involved in the control of collagen fibril assembly. Using in situ mutagenesis we have determined that a single glutamate (Glu-180) within decorin is critical for its interaction with type I collagen thereby localizing the probable point of interaction of this TGF-beta-binding protein with the matrix. Within the integrin-binding glycoprotein, bone sialoprotein (BSP), we have mapped both its strong apatite-binding domains and the peptide domains required for RGD- independent cell attachment properties. Collaborative studies have also shown that BSP is an intriguing marker for those cancers that not only frequently present with microcalcifications within the primary lesions, but also have an high propensity of metastasizing to bone. We have also had some success determining conditions that cause temporal shifts in matrix mineralization using common hormones and expect that this approach will allow us to to search for those elements that control the mineralization of bones and dentin.